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Biomedical subjects

S S Epstein

Publications and source records attributed to S S Epstein.

At least 19 recordsLinked to original sources
PubMed1979

Effects of piperonyl butoxide on the toxicity and hepatocarcinogenicity of 2-acetylaminofluorene and 4-acetylaminobiphenyl, and their n-hydroxylated derivatives, following administration of newborn mice.

Neonatal ICR/Ha mice were injected subcutaneously with a single dose of 25, 50 and 100 microgram of 4-acetylaminobiphenyl (AAB), N-hydroxy-4-acetylaminobiphenyl (N-OH-AAB), 2-acetylaminofluorene (AAF), or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) alone or together with 2,5% piperonyl butoxide (PB) in tricaprylin, negative control groups were injected with tricaprylin, and positive control groups were injected with 30 microgram of 7,12-dimethylbenz(a)anthracene (DMBA), alone or with PB. PB induced synergistic toxicity in the various groups of mice injected with the nonhydroxylated and hydroxylated amine carcinogens, or with DMBA, as compared with groups injected with carcinogen alone. AAB, N-OH-AAB, AAF, and N-OH-AAF all induced dose-related hepatocarcinogenicity in male, but not female mice, which was not consistently influenced by concomitant administration of PB. DMBA control groups developed pulmonary adenomas and lymphomas in both sexes, and hepatomas in males, whose incidences were not modified by PB.

2-Acetylaminofluorene↗
PubMed1978

Evidence of DNA repair in the guinea pig pancreas, in vivo and in vitro, following exposure to N-methyl-N-nitrosourethane.

The nature of DNA damage induced by N-methyl-N-nitrosourethane (NMUT) in the guinea pig pancreas, both in vitro and in vivo, and subsequent repair was investigated by alkaline sucrose density gradient analysis, using a non-radioactive fluorimetric procedure for DNA determination in gradient fractions. In vitro exposure of pancreatic slices to 20 mM NMUT for 30 min damaged DNA to less than 2.24 . 10(6) dalton fragments. However, incubation of NMUT-treated slices for 3 h in a fresh medium resulted in the repair of most of DNA damage, as indicated by the conversion of low molecular weight DNA fragments into heavy DNA of molecular weight comparable to DNA from control slices. Additionally, a single administration of NMUT (30 mg/kg, i.p.) to guinea pigs induced extensive DNA damage, to less than 2.24 . 10(6) dalton fragments in the pancreas within 4 h; similar DNA damage was observed in the liver. However, in the pancreas and liver of guinea pigs sacrificed at increasing intervals after NMUT administration, there was a gradual conversion of shortened DNA fragments to heavy high molecular weight DNA, indicating repair of DNA damage. It appears that most of DNA damage in the pancreas and liver was repaired by 14 and 7 days, respectively, following NMUT administration.

Animals↗
PubMed1978

Kepone--hazard evaluation.

Kepone is a persistent chlorinated hydrocarbon pesticide which is no longer manufactured in the U.S.A., its uses having been cancelled on April 11, 1977; previous food uses included control of the banana root borer, and non-food uses included control of tobacco wireworm, ants, and cockroaches. An adduct of Kepone, Kelevan, is now distributed by Spiess and Sohn, Chemische Fabrik, Germany, with an as yet unknown manufacturer, for control of the Colorado potato beetle in Eastern Europe and Ireland, and for control of the banana root borer in the cameroons, Caribbean, and South America. Kepone is acutely toxic and induces cumulative and delayed toxicity, neurotoxicity, and reproductive impairment, in a wide range of species including birds, rodents and humans; it is also carcinogenic in rodents. Extensive environmental dispersion, with major evidence of aquatic toxicity has been demonstrated following its recent manufacture in Hopewell, Virginia, U.S.A.

Animals↗
PubMed1977

Quantitation of dimethylnitrosamine in the whole mouse after biosynthesis in vivo from trace levels of precursors.

A simple and highly sensitive procedure is described for the recovery and quantitative identification of nanogram quantities of preformed N-nitroso compounds in the whole mouse. This procedure has also been applied to the quantitation of N-nitroso compounds after they have been biosynthesized from trace amounts of precursors. The whole animal is frozen in liquid nitrogen and homogenized to a frozen powder; the powder is then extracted and analyzed by a thermal energy analyzer interfaced to a gas-liquid and a high-pressure liquid chromatograph.

Animals↗
PubMed1977

Hepatocarcinogenic effects of N-nitroso-N-methylurea in guinea pigs.

Intragastric administration of N-nitroso-N-methylurea to strain 13 male guinea pigs, at a weekly dosage of 7.5 mg/kg for 15 weeks and then twice weekly for a subsequent 15 weeks, induced high toxicity, as evidenced by weight loss and mortality and a high incidence of malignant neoplasms, over a total observational period of 40 weeks. The neoplasms included hepatic angiosarcomas, cholangiocarcinomas, and generalized lymphoblastic lymphomas.

Adenoma, Bile Duct↗
PubMed1977

Metabolism of benzo(a)pyrene by guinea pig pancreatic microsomes.

The in vitro microsomal metabolism of the strain 13 guinea pig pancreas was investigated by determining the benzo(a)pyrene (BP) hydroxylase activity in the 9000 x g supernatant and microsomal pellet. BP hydroxylase activity in both 9000 x g supernatant and microsomal pellet of the pancreas was less than 1% of the activity in the respective liver fractions, However, pretreatment of animals with methylcholanthrene or BP at 20 mg/kg, for either 1 day or 3 consecutive days, markedly enhanced the BP hydroxylase activity of pancreatic microsomes over that of controls; the induction in the liver microsomes was less than 2-fold over that of controls. The hydroxylation of BP by pancreatic microsomes was linear with time over a 30-min period, with the rate of hydroxylation dependent on both the enzyme and substrate concentrations.

Animals↗
PubMed1976

Effects of N-methyl-N-nitrosourethane on DNA synthesis in the guinea pig pancreas.

The effects of N-methyl-N-nitrosourethane (NMUT) on pancreatic DNA synthesis were investigated at sequential intervals following gavage of Hartley guinea pigs with a single dose of 30 mg/kg. There was a highly significant stimulation of DNA synthesis, as evidenced by increased incorporation of [3H] methyl-thymidine ([3H]TdR), throughout the whole pancreas and particularly in the duodenal segment, at 4 h following NMUT administration, thereafter, DNA synthesis declined sharply up to 24 h, and then recovered gradually to control levels from 24--96 h. DNA synthesis stimulated by NMUT was suppressed by hydroxyurea (HU), and hence is likely to represent replicative, rather than repair, synthesis.

Animals↗
PubMed1976

Drinking water and cancer mortality in Louisiana.

Multivariant regression analysis indicates a statistically significant relation between cancer mortality rates in Louisiana and drinking water obtained from the Missippi River. This is true for total cancer, cancer of the urinary organs, and cancer of the gastrointestinal tract.

Breast Neoplasms↗
PubMed1976

DNA repair synthesis in guinea pig pancreatic slices following in vitro exposure to N-nitrosomethylurethane.

The incorporation of thymidine into DNA in the presence of hydroxyurea (HU) by guinea pig pancreatic slices following exposure to N-nitrosomethylurethane (NMUT) was used to follow DNA repair synthesis. HU was used to suppress normal replicative DNA synthesis. Slices from the duodenal segment of the pancreas were exposed for periods of 15 to 90 min to NMUT at concentrations of 2 to 20 mM, then incubated in tritiated thymidine ([H3]-TdR) free of carcinogen, and radioactivity in DNA was determined. NMUT induced a a dose- and time-dependent increase in HU-insensitive thymidine incorporation. This stimulated incorporation, which could be attributed to repair synthesis, occurred immediately following the treatment and was largely complete within 3 h.

Animals↗